For years scientists have dreamed of developing a genuine memory booster, a drug that could tune the brain's biological search engine so that it's better at retrieving not only recently learned facts, like last night's dinner menu, but details that seem all but lost in the fog of time, like childhood classmates' names and antics.
Such a substance would have obvious appeal — for people at risk of dementia, to name just one group — but the search has been very slow going. Stimulants like caffeine and nicotine can sharpen the memory, but like other temporary enhancers, they need to be taken when the information is learned or retrieved to make a difference.
Now, researchers in Israel and New York report that they have been able to strengthen memories formed well in the past, using a brain substance involved in anchoring and maintaining the memory in the first place. The finding, reported last week in the journal Science, is one of two recent studies in which neuroscientists used molecules active in memory formation to, in effect, goose the system and improve recall. Both studies were conducted in rats, which provide a very rough model for human memory.
"The idea that an older memory can be strengthened is a novel and exciting finding," said Jim McGaugh, a neuroscientist at the University of California, Irvine, who was not involved in the research. "But it also raises the question: How does this work? And, does it apply to all memories?"
In the study published last week, researchers at the Weizmann Institute of Science in Rehovot, Israel, and the S.U.N.Y. Downstate Medical Center in Brooklyn found that giving rats an infusion of PKM-zeta, an enzyme known to be active in storing memories, strongly sharpened their aversion to drinking a sweet liquid. The animals had learned, six days earlier, that the liquid could make them sick.
Six days is a long time for a rat, said Todd C. Sacktor, a neuroscientist at Downstate and an author of the paper. "For years we thought that once a memory goes into long-term storage, no one could do anything with it; it would just gradually fade. Well, apparently that's not true."
The researchers argue that the substance they injected may act on almost any memory that the brain tries to retrieve while the drug is active. "It is unlikely that such memory, though enhanced, will not be subjected so some processes of weakening over time," another of the authors, Yadin Dudai of the Weizmann Institute, said in an e-mail. "We do not think that we will be able to create the analogue of Funes, that famous fictional protagonist of Jorge Luis Borges who remembered forever every detail he ever encountered."
In a paper published several weeks earlier, however, researchers at Mount Sinai School of Medicine showed that they could make a specific memory last a long time — again, by using a brain substance involved in the initial learning. Rats that received an injection of the substance, called a growth factor, immediately after learning how to avoid a foot shock in their cage retained a memory of the experience that was as fresh a week or more later as on the first day.
"This is a substance that's involved in the natural regulation of memory consolidation, and an injection significantly slows down forgetting," said Cristina M. Alberini, a neuroscientist at Mount Sinai and a co-author of the earlier study, published in the journal Nature.
Turning these findings into useful drugs is another matter altogether, experts say. Researchers still have little idea of how these experimental drugs sharpen memories, whether they affect only specific memories, or what the risks are. "I've been working on memory enhancement since 1957, and I don't know of a single drug that came out of work with animals that was later developed for humans," said Dr. McGaugh. "It's very interesting work; now let's see where it goes."